The costs for solar photovoltaics, wind, and battery storage have dropped markedly since 2010, however, many recent studies and reports around the world have not adequately captured such dramatic ...decrease. Those costs are projected to decline further in the near future, bringing new prospects for the widespread penetration of renewables and extensive power-sector decarbonization that previous policy discussions did not fully consider. Here we show if cost trends for renewables continue, 62% of China's electricity could come from non-fossil sources by 2030 at a cost that is 11% lower than achieved through a business-as-usual approach. Further, China's power sector could cut half of its 2015 carbon emissions at a cost about 6% lower compared to business-as-usual conditions.
When resource demand increases and decreases rapidly, container clusters in the cloud environment need to respond to the number of containers in a timely manner to ensure service quality. Resource ...load prediction is a prominent challenge issue with the widespread adoption of cloud computing. A novel cloud computing load prediction method has been proposed, the Double-channel residual Self-attention Temporal convolutional Network with Weight adaptive updating (DSTNW), in order to make the response of the container cluster more rapid and accurate. A Double-channel Temporal Convolution Network model (DTN) has been developed to capture long-term sequence dependencies and enhance feature extraction capabilities when the model handles long load sequences. Double-channel dilated causal convolution has been adopted to replace the single-channel dilated causal convolution in the DTN. A residual temporal self-attention mechanism (SM) has been proposed to improve the performance of the network and focus on features with significant contributions from the DTN. DTN and SM jointly constitute a dual-channel residual self-attention temporal convolutional network (DSTN). In addition, by evaluating the accuracy aspects of single and stacked DSTNs, an adaptive weight strategy has been proposed to assign corresponding weights for the single and stacked DSTNs, respectively. The experimental results highlight that the developed method has outstanding prediction performance for cloud computing in comparison with some state-of-the-art methods. The proposed method achieved an average improvement of 24.16% and 30.48% on the Container dataset and Google dataset, respectively.
Circular RNAs (circRNAs) are a class of long, non-coding RNAs molecules that shape a covalently closed continuous loop which have no 5′–3′ polarity and contain no polyA tail. CircRNAs also possess ...relatively jarless framework and are highly tissue-specific expressed in the eukaryotic transcriptome. Emerging evidences have discovered that thousands of endogenous circRNAs are present in mammalian cells and they mediate gene expression at the transcriptional or post-transcriptional level by binding to microRNAs or other molecules and then inhibit their function. Similarly, increasing evidence indicates that circRNAs may play a role in the development of several types of diseases, including atherosclerotic vascular disease risk, neurological disorders, prion diseases, osteoarthritis and diabetes. Furthermore, circRNAs exhibit aberrant expression in multiform types of cancer, including colorectal cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma. And based on the function of circRNAs in cancer, we believe that circRNAs may serve as diagnostic or tumor promising biomarkers. Moreover, it will provide a new therapeutic target for the treatment of cancer.
In this study, we examined the Ca2+‐permeable Piezo1 channel, a newly identified mechanosensing ion channel, in human dental pulp‐derived mesenchymal stem cells (MSCs) and hypothesized that ...activation of the Piezo1 channel regulates MSC migration via inducing ATP release and activation of the P2 receptor purinergic signaling. The Piezo1 mRNA and protein were readily detected in hDP‐MSCs from multiple donors and, consistently, brief exposure to Yoda1, the Piezo1 channel‐specific activator, elevated intracellular Ca2+ concentration. Yoda1‐induced Ca2+ response was inhibited by ruthenium red or GsMTx4, two Piezo1 channel inhibitors, and also by Piezo1‐specific siRNA. Brief exposure to Yoda1 also induced ATP release. Persistent exposure to Yoda1 stimulated MSC migration, which was suppressed by Piezo1‐specific siRNA, and also prevented by apyrase, an ATP scavenger, or PPADS, a P2 generic antagonist. Furthermore, stimulation of MSC migration induced by Yoda1 as well as ATP was suppressed by PF431396, a PYK2 kinase inhibitor, or U0126, an inhibitor of the mitogen‐activated protein kinase MEK/ERK signaling pathway. Collectively, these results suggest that activation of the Piezo1 channel stimulates MSC migration via inducing ATP release and subsequent activation of the P2 receptor purinergic signaling and downstream PYK2 and MEK/ERK signaling pathways, thus revealing novel insights into the molecular and signaling mechanisms regulating MSC migration. Such findings provide useful information for evolving a full understanding of MSC migration and homing and developing strategies to improve MSC‐based translational applications.
A, Exposure to Yoda1, the Piezo1 channel‐specific activator, stimulates human dental pulp mesenchymal stem cell migration in wound healing assay; B, the underlying signaling mechanisms.
Biodiversity across multiple trophic levels is required to maintain multiple ecosystem functions. Yet it remains unclear how multitrophic diversity and species interactions regulate ecosystem ...multifunctionality. Here, combining data from 9 different trophic groups (including trees, shrubs, herbs, leaf mites, small mammals, bacteria, pathogenic fungi, saprophytic fungi, and symbiotic fungi) and 13 ecosystem functions related to supporting, provisioning, and regulating services, we used a multitrophic perspective to evaluate the effects of elevation, diversity, and network complexity on scale‐dependent subalpine forest multifunctionality. Our results demonstrated that elevation and soil pH significantly modified species composition and richness across multitrophic groups and influenced multiple functions simultaneously. We present evidence that species richness across multiple trophic groups had stronger effects on multifunctionality than species richness at any single trophic level. Moreover, biotic associations, indicating the complexity of trophic networks, were positively associated with multifunctionality. The relative effects of diversity on multifunctionality increased at the scale of the larger community compared to a scale accounting for neighboring interactions. Our results highlight the paramount importance of scale‐ and context‐dependent multitrophic diversity and interactions for a better understanding of mountain ecosystem multifunctionality in a changing world.
Salt stress can significantly affect plant growth and agricultural productivity. Receptor-like kinases (RLKs) are believed to play essential roles in plant growth, development, and responses to ...abiotic stresses. Here, we identify a receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase 1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative stress tolerance. Our results show that STRK1 anchors and interacts with CatC at the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210 and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits higher catalase activity both in vitro and in planta, and salt stress enhances STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants, STRK1-overexpressing plants exhibited higher catalase activity and lower accumulation of H2O2 as well as higher tolerance to salt and oxidative stress. Our findings demonstrate that STRK1 improves salt and oxidative tolerance by phosphorylating and activating CatC and thereby regulating H2O2 homeostasis. Moreover, overexpression of STRK1 in rice not only improved growth at the seedling stage but also markedly limited the grain yield loss under salt stress conditions. Together, these results offer an opportunity to improve rice grain yield under salt stress.
Transient receptor potential melastatin 2 (TRPM2) channel activation by reactive oxygen species (ROS) plays a critical role in delayed neuronal cell death, responsible for postischemia brain damage ...via altering intracellular Zn2+ homeostasis, but a mechanistic understanding is still lacking. Here, we showed that H2O2 induced neuroblastoma SH‐SY5Y cell death with a significant delay, dependently of the TRPM2 channel and increased Zn2+i, and therefore used this cell model to investigate the mechanisms underlying ROS‐induced TRPM2‐mediated delayed cell death. H2O2 increased concentration‐dependently the Zn2+i and caused lysosomal dysfunction and Zn2+ loss and, furthermore, mitochondrial Zn2+ accumulation, fragmentation, and ROS generation. Such effects were suppressed by preventing poly(adenosine diphosphate ribose, ADPR) polymerase‐1‐dependent TRPM2 channel activation with PJ34 and 3,3′,5,5′‐tetra‐tert‐butyldiphenoquinone, inhibiting the TRPM2 channel with 2‐aminoethoxydiphenyl borate (2‐APB) and N‐(p‐amylcinnamoyl)anthranilic acid, or chelating Zn2+ with N,N,N,N‐tetrakis(2‐pyridylmethyl)‐ethylenediamine (TPEN). Bafilomycin‐induced lysosomal dysfunction also resulted in mitochondrial Zn2+ accumulation, fragmentation, and ROS generation that were inhibited by PJ34 or 2‐APB, suggesting that these mitochondrial events are TRPM2 dependent and sequela of lysosomal dysfunction. Mitochondrial TRPM2 expression was detected and exposure to ADPR‐induced Zn2+ uptake in isolated mitochondria, which was prevented by TPEN. H2O2‐induced delayed cell death was inhibited by apocynin and diphenyleneiodonium, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase (NOX) inhibitors, GKT137831, an NOX1/4‐specific inhibitor, or Gö6983, a protein kinase C (PKC) inhibitor. Moreover, inhibition of PKC/NOX prevented H2O2‐induced ROS generation, lysosomal dysfunction and Zn2+ release, and mitochondrial Zn2+ accumulation, fragmentation and ROS generation. Collectively, these results support a critical role for the TRPM2 channel in coupling PKC/NOX‐mediated ROS generation, lysosomal Zn2+ release, and mitochondrial Zn2+ accumulation, and ROS generation to form a vicious positive feedback signaling mechanism for ROS‐induced delayed cell death.
Transient receptor potential melastatin 2 (TRPM2) channel activation by reactive oxygen species (ROS) is critically responsible for delayed neuronal cell death, responsible for postischemia brain damage via altering intracellular Zn2+ homeostasis. In this study, we provide evidence to support that the TRPM2 channel plays a critical role in forming a vicious positive feedback signaling mechanism for ROS‐induced delayed cell death.
We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were ...laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.
Background
This study examines the predictive value of a novel systemic immune‐inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients.
Methods
A ...total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long‐term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure.
Results
An optimal SII cut‐off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43‐2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09‐1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28‐2.99), MACE (HR: 1.65; 95% CI: 1.36‐2.01) and total major events (HR: 1.53; 95% CI: 1.32‐1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C‐index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05).
Conclusions
SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.
Microglial cells are crucial in maintaining central nervous system (CNS) homeostasis and mediating CNS disease pathogenesis. Increasing evidence supports that alterations in the mechanical properties ...of CNS microenvironments influence glial cell phenotypes, but the mechanisms regulating microglial cell function remain elusive. Here, we examined the mechanosensitive Piezo1 channel in microglial cells, particularly, how Piezo1 channel activation regulates pro‐inflammatory activation and production of pro‐inflammatory cytokines, using BV2 and primary microglial cells. Piezo1 expression in microglial cells was detected both at mRNA and protein levels. Application of Piezo1 channel activator Yoda1 induced Ca2+ flux to increase intracellular Ca2+ concentration that was reduced by treatment with ruthenium red, a Piezo1 inhibitor, or Piezo1‐specific siRNA, supporting that Piezo1 functions as a cell surface Ca2+‐permeable channel. Priming with lipopolysaccharide (LPS) induced microglial cell activation and production of TNF‐α and IL‐6, which were inhibited by treatment with Yoda1. Furthermore, LPS priming induced the activation of ERK, p38 MAPKs, and NF‐κB. LPS‐induced activation of NF‐κB, but not ERK and p38, was inhibited by treatment with Yoda1. Yoda1‐induced inhibition was blunted by siRNA‐mediated depletion of Piezo1 expression and, furthermore, treatment with BAPTA‐AM to prevent intracellular Ca2+ increase. Collectively, our results support that Piezo1 channel activation downregulates the pro‐inflammatory function of microglial cells, especially production of TNF‐α and IL‐6, by initiating intracellular Ca2+ signaling to inhibit the NF‐κB inflammatory signaling pathway. These findings reveal Piezo1 channel activation as a previously unrecognized mechanism regulating microglial cell function, raising an interesting perspective on targeting this molecular mechanism to alleviate neuroinflammation and associated CNS pathologies.
Main Points
Piezo1 is expressed in microglial cells as a Ca2+‐permeable channel on the cell surface
Piezo1 channel activation inhibits LPS‐induced activation of the NF‐κB pathway and production of TNF‐α and IL‐6